The long term goal of this research is to determine the basic structural and functional characteristics of factor XIII molecules and to correlate these with the enzymatic activity of factor XIIIa in physiologic and pathologic processes. Factor XIII is essential for normal hemostasis and patients who are deficient have several hemorragic problems. Moreover, factor XIII may also have an imporant function in the general processes of cell proliferation, including wound healing and tissue repair, tumor growth and metatasis, and atherosclerosis. The specific aims of this project are in four areas: metabolism, biochemical characterization, immunochemical characterization, and patient studies. Metabolic studies include work on the biosynthesis and catabolism in a guinea pig model, and studies on the effects of factor XIII on fibroblasts and endothelial cells, both in tissue culture and in a guinea pig model. Biochemical studies include characterization of thrombin interaction with factor XIII and factor XIII interaction with fibrin(ogen). These studies will use radiolabeled, purified proteins for affinity chromatography and gradient ultracentrifugation. Immunochemical characterization will be done using monoclonal antibodies to map the topography of factor XIII molecules. Patient studies will include in vitro experiments in which trace labeled factor XIII proteins are added to whole blood or plasma. Allelic distribution of factor XIII will be studied in plasma from bone marrow transplant patients, and families with factor XIII deficiency will also be studied.